[Cancer Research 38, 4486-4495, December 1, 1978]
© 1978 American Association for Cancer Research
Elevation of Hepatic Glutathione S-Transferase Activities and Protection against Mutagenic Metabolites of Benzo(a)pyrene by Dietary Antioxidants1
Ann M. Benson,
Robert P. Batzinger,
Suh-Yun L. Ou,
Ernest Bueding,
Young-Nam Cha and
Paul Talalay2
Department of Pharmacology and Experimental Therapeutics, The Johns Hopkins University School of Medicine [A. M. B., E. B., P. T.], and Department of Pathobiology, The Johns Hopkins University School of Hygiene and Public Health [R. P. B., S-Y. L. O., E. B., Y-N. C.], Baltimore, Maryland 21205
Addition of either 2(3)-tert-butyl-4-hydroxyanisole (BHA) or 1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline (ethoxyquin) to the diet greatly decreases the levels of mutagenic metabolites of benzo(a)pyrene in CD-1 mice. (R. P. Batzinger, S-Y. L. Ou, and E. Bueding, Cancer Res., 38:000, 1978). The mutagenic activity of the urinary metabolites of benzo(a)pyrene is markedly reduced in the presence of glutathione together with the liver cytosols of rats or mice fed on a diet containing BHA. The liver cytosols of mice and rats maintained on control diets are much less effective in this respect. Dietary BHA causes increases in mouse and rat hepatic glutathione S-transferase (EC 2.5.1.18) specific activities with 1,2-dichloro-4-nitrobenzene, 1-chloro-2,4-dinitrobenzene, p-nitrobenzylchloride, and 
5-androstene-3,17-dione. In the mouse the increases are larger (5- to 10-fold) and are dependent on the dose and duration of administration of BHA. Increases in these glutathione S-transferase specific activities were also observed in mouse hepatic cytosols after feeding of ethoxyquin. Direct addition of reduced glutathione and purified glutathione S-transferases A and B obtained from rat liver to the mutagenicity assay system mimicked the effect of the rodent cytosols. Since BHA and ethoxyquin are known to reduce the neoplastic effects of a variety of potent carcinogens, we suggest that the protective effects of these antioxidants may be accounted for, at least in part, by their ability to elevate the glutathione S-transferases. These enzymes inactivate arene oxides and other hydrophobic electrophiles by catalyzing their conjugation with glutathione.
1 Supported by NIH Grants GM 16492, AI 08022, AM 07422, and CA 18251 and by the Edna McConnel Clark Foundation. A preliminary account of this work has been published (4).
2 To whom requests for reprints should be addressed, at Department of Pharmacology and Experimental Therapeutics, The Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, Md. 21205.
Received 4/26/78.
Accepted 8/23/78.
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Copyright © 1978 by the American Association for Cancer Research.
